Spontaneous Spatial Correlation of Elastic Modulus in Jammed Epithelial Monolayers Observed by AFM

Abstract

For isolated single cells on a substrate, the intracellular stiffness, which is often measured as the Young’s modulus, E, by atomic force microscopy (AFM), depends on the substrate rigidity. However, little is known about how the E of cells is influenced by the surrounding cells in a cell population system in which cells physically and tightly contact adjacent cells. In this study, we investigated the spatial heterogeneities of E in a jammed epithelial monolayer in which cell migration was highly inhibited, allowing us to precisely measure the spatial distribution of E in large-scale regions by AFM. The AFM measurements showed that E can be characterized using two spatial correlation lengths: the shorter correlation length, l_S, is within the single cell size, whereas the longer correlation length, l_L, is longer than the distance between adjacent cells and corresponds to the intercellular correlation of E. We found that l_L decreased significantly when the actin filaments were disrupted or calcium ions were chelated using chemical treatments, and the decreased l_L recovered to the value in the control condition after the treatments were washed out. Moreover, we found that l_L decreased significantly when E-cadherin was knocked down. These results indicate that the observed long-range correlation of E is not fixed within the jammed state but inherently arises from the formation of a large-scale actin filament structure via E-cadherin-dependent cell-cell junctions.